Patterns of Late Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with T-Cell Prolymphocytic Leukemia

Abstract

Initial treatment with the monoclonal anti-CD52 antibody alemtuzumab induces responses in the majority of patients with T-cell prolymphocytic leukemia (T-PLL). In eligible patients, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an option to consolidate hematological remissions. Here, we report our experience with 10 patients who received allo-HSCT against T-PLL. Notably, 3 patients with complete remission at transplantation and durable full-donor chimerism relapsed at months 12, 59, and 84 after transplantation, respectively. This relapse was associated with rapid progressive leukemia in 1 patient and extralymphatic lymphoma growth in the other 2. Despite CD52 positivity at relapse, alemtuzumab retreatment, donor lymphocyte infusions, and/or chemotherapy including salvage therapy, allo-HSCT yielded a transient partial response, only. Alemtuzumab induction and consolidative allo-HSCT enabled prolonged disease-free survival in these patients but failed to procure cure.

What to Look Out for when Transplanting T-Cell Prolymphocytic Leukemia

“…A PCR-based assessment of minimal residual disease (MRD) kinetics was reported by Sellner et al [12] and confirmed the presence of graft-versus-leukemia effects in T-PLL. In line with the results by Shumilov et al [11], they observed a significant reduction of MRD levels upon immunomodulation in 7/10 patients, but with complete MRD clearance in only 2 patients.…”

“…The authors observed PD (5/10) or NRM (5/10) in all 10 patients and the 2-year OS of 30% and the 4-year OS of 20% was below the OS in the prospective EBMT series [8]. The high NRM in this series [11] was primarily caused by fatal infections, underlining the relevance of infectious complications in the post-transplantation management. CMV reactivations were observed in 6 (60%) patients with a lethal infection in 1 case.…”

“…Given these data, is there something new to learn from retrospective data on allo-HSCT in T-PLL? In this issue of Acta Haematologica , Shumilov et al [11] report a retrospective single-center analysis of 10 T-PLL patients who received an allo-HSCT between 2004 and 2019 after a median time from diagnosis to transplantation of 6 months. All 10 patients had an alemtuzumab-containing induction or re-induction regimen.…”

“…Although most relapses develop within the first 2 years after allo-HSCT [4, 8] and stable long-lasting (>10 years) remissions are described in T-PLL [10], Shumilov et al [11] illustrate that late progression is not uncommon [5, 11]. In these cases, persistence of T-PLL often remains undetected by conventional monitoring of donor chimerism.…”

Mutations in PIGA cause a CD52‐/GPI‐anchor‐deficient phenotype complicating alemtuzumab treatment in T‐cell prolymphocytic leukemia

“…1 Relapsing disease is usually highly refractory both to conventional chemotherapy and retreatment with alemtuzumab. 1,4,5 Molecular mechanisms underlying resistance to alemtuzumab are largely unknown, but may include down-regulation of its target CD52 on the surface of the leukemic cells. 6,7 However, the molecular reasons for this immunophenotypic change and its clinical significance remain unclear.…”